Abstract Nigerian women face one of the worst prognosis in the world when diagnosed with cervical cancer, and this prognosis worsens with HIV infection. In addition to poor screening and follow-up, one major reason for the high prevalence and incidence of cervical cancer is due to the large number of HIV-infected individuals with Nigeria ranking second in the world in HIV burden, behind South Africa.3,4 Our long-term goal is to understand the role of epigenetic biomarkers in HIV-associated cervical cancer and to develop potential targeted interventions to improve prevention, early detection of invasive cervical cancer in Nigeria and similar settings in Africa. Identification of epigenetic markers predictive of progression to invasion will also provide opportunities for developing future therapeutic targets for the management of women with cervical dysplasia and cancer. The molecular mechanisms by which long-term HIV infection may promote cervical carcinogenesis remains largely unknown. Epigenetic alterations, a hallmark of cancer, have been studied for their mechanistic role and early detection and prognostic biomarkers of cervical cancer with some promising findings. However, little has been done in HIV-associated cervical cancer patients, in particular, in LIMCs, such as Nigeria where HIV infection is highly prevalent. We hypothesize that HIV infected women with cervical cancer will have different epigenetic biomarkers compared to the non-HIV infected women or cancer- free HIV-positive women, and such biomarkers will play important role in cancer progression, leading to different histopathologic grading and other prognostic features. Such biomarkers in precancerous cervical lesions may also predict risk of progression to invasive cervical cancer. In Nigeria?s Lagos and Jos medical centers, over 5 years, we aim to: (1) Identify epigenetic biomarkers in 100 HIV infected women who have invasive cervical cancer as compared to 100 HIV negative women with invasive cervical cancer and also to 100 HIV-positive cancer-free women. (2) Investigate the association of HIV- positive cervical cancer epigenetic biomarkers with prognostic factors in the Aim 1 cohort. (3) Examine the epigenetic biomarkers identified in Aim 1 along the cervical dysplasia continuum in 300 HIV-positive women to explore what proportion of women with such biomarkers will progress to higher grades of dysplasia or invasive cervical cancer.